Corneal damage causes significant vision loss in the general world population, second only to cataracts. Corneal replacement is a developing technology that is rapidly becoming a necessity for many patients. Many of the reasons for corneal replacement therapies include scarring from disease (e.g. herpes infection) or complications from LASIK;hereditary problems (e.g., Fuch's disease) and complications from other surgeries (e.g., cataracts). Current strategies employed for corneal grafting make use of allogenic or synthetic materials. These strategies are only partially effective, however, and may stimulate host immune responses that result in tissue rejection. In addition, there is the potential for transfer of diseases from unhealthy donor organs. These issues are compounded by the growing use of corrective eye surgery which renders corneas unsuitable for grafting which will further impact the availability of acceptable allogenic supplies. A cornea replacement that alleviates these issues would be a clinically important advance, and this is the goal of the present exploratory proposal (R21). The hypothesis is that a unique protein-biomaterial system based on silk fibroin can be bioengineered to match cornea functional requirements in combination with cornea-specific cells, to thus serve as a cornea replacement. The proposed system will exploit the novel material features of silk fibroin that include: slow degradation, biocompatibility, full optical transparency and mechanical durability for handling, suturing and ocular pressure requirements. The research team has the required background with silk material designs to meet the material performance requirements and the experience with the cornea cell biology to characterize the material-cell interactions outlined in this project. We will: (Aim #1) prepare and characterize the required protein films and assess cornea cell interactions (both rabbit and human) with these materials, and (Aim #2) assess a system concept that will mimic the native cornea in terms of a lamellar structure incorporating rabbit fibroblast, epithelial and endothelial cells with their appropriate extracellular matrix deposition. The outcome of this effort will be initial cornea designs to move forward into an R01 for animal studies related to cornea replacements. An interdisciplinary team has been assembled to meet the challenges and all of the required analytical tools are in place to address the experimental scope. A cornea tissue system that slowly degrades to allow for host native tissue replacement would offer a significant advancement in corneal transplantation technology. An R21 mechanism is proposed as this is a new exploratory initiative, building upon a solid foundation of prior research in both laboratories, but towards an entirely new tissue construct with new challenges and complexities. PUBLIC HEALTH RELEVANCE: Corneal damage causes significant vision loss in the general world population;it is second only to cataracts. There is a need to develop a readily available corneal tissue supply for transplantation in both the US and the rest of the world to meet the challenge of combating this prevalent form of vision loss. A unique protein-biomaterial system constructed from silk fibroin and cornea-specific cells can be bioengineered to serve as a total cornea replacement. The proposed system will exploit the novel biomaterial features of silk fibroin to produce a readily available supply of corneal tissue that will meet, or exceed, the biocompatibility and material properties of current allogenic transplant tissue.